Abstract In this study the effect of the cytostatic acting sesquiterpene lactone eupatoriopicrin, isolated from Eupatorium cannabinum L., on gluthathione (GSH) levels in liver and tumour tissue of the mouse is described. C57Bl mice, bearing a solidly growing Lewis Lung carcinoma or a FIO 26 fibrosarcoma, with a volume between 500–1000 μL, were injected with eupatoriopicrin 20 or 40 mg/kg, intraperitoneally (i.p.) or intravenously (i.v.). At different time points, between 0–48 h after administration, the GSH content in liver and tumour tissue was determined. A dose dependent reduction of the GSH content was found. No difference in reduction was seen between i.p. and i.v. administration, but the route of administration appeared to be of great importance regarding acute toxicity: 40 mg/kg i.p. was lethal within 48 h, whereas mice receiving the same dose i.v. survived for over three months.
Coenzyme A (CoA) is an essential metabolite, synthesized from vitamin B5 by the subsequent action of five enzymes: PANK, PPCS, PPCDC, PPAT and DPCK. Mutations in Drosophila dPPCS disrupt female fecundity and in this study we analyzed the female sterile phenotype of dPPCS mutants in detail.We demonstrate that dPPCS is required for various processes that occur during oogenesis including chorion patterning. Our analysis demonstrates that a mutation in dPPCS disrupts the organization of the somatic and germ line cells, affects F-actin organization and results in abnormal PtdIns(4,5)P2 localization. Improper cell organization coincides with aberrant localization of the membrane molecules Gurken (Grk) and Notch, whose activities are required for specification of the follicle cells that pattern the eggshell. Mutations in dPPCS also induce alterations in scutellar patterning and cause wing vein abnormalities. Interestingly, mutations in dPANK and dPPAT-DPCK result in similar patterning defects.Together, our results demonstrate that de novo CoA biosynthesis is required for proper tissue morphogenesis.
Abstract In this study the possible cytostatic effects of eupatoriopicrin, a sesquiterpene lactone isolated from Eupatorium cannabinum L., against the fibrosarcoma FIO 26 have been investigated. This solidly growing tumour was transplanted subcutaneously in C57Bl mice. Eupatoriopicrin was administered intraperitoneally (as single as well as repeated doses) as a solution in 20% v/v ethanol. Different doses and dosage schedules were used and compared with control conditions. A dose dependent growth delay of the tumour was found. The treating volume of the tumour was about 500 μl. Two clinically applied chemotherapeutics, doxorubicin and cyclophosphamide, were used as reference compounds.
